First analysis of anisotropic flow with Lee--Yang zeroes

We report on the first analysis of directed and elliptic flow with the new method of Lee--Yang zeroes. Experimental data are presented for Ru+Ru reactions at 1.69 AGeV measured with the FOPI detector at SIS/GSI. The results obtained with several methods, based on the event-plane reconstruction, on Lee--Yang zeroes, and on multi-particle cumulants (up to 5th order) applied for the first time at SIS energies, are compared. They show conclusive evidence that azimuthal correlations between nucleons and composite particles at this energy are largely dominated by anisotropic flow.Comment: 5 pages, 3 figures, submitted to Phys. Rev. C Rapid Co

Identification of baryon resonances in central heavy-ion collisions at energies between 1 and 2 AGeV

The mass distributions of baryon resonances populated in near-central collisions of Au on Au and Ni on Ni are deduced by defolding the $p_t$ spectra of charged pions by a method which does not depend on a specific resonance shape. In addition the mass distributions of resonances are obtained from the invariant masses of $(p, \pi^{\pm})$ pairs. With both methods the deduced mass distributions are shifted by an average value of -60 MeV/c$^2$ relative to the mass distribution of the free $\Delta(1232)$ resonance, the distributions descent almost exponentially towards mass values of 2000 MeV/c^2. The observed differences between $(p, \pi^-)$ and $(p, \pi^+)$ pairs indicate a contribution of isospin $I = 1/2$ resonances. The attempt to consistently describe the deduced mass distributions and the reconstructed kinetic energy spectra of the resonances leads to new insights about the freeze out conditions, i.e. to rather low temperatures and large expansion velocities.Comment: 30 pages, 13 figures, Latex using documentstyle[12pt,a4,epsfig], to appear in Eur. Phys. J.

Excitation function of elliptic flow in Au+Au collisions and the nuclear matter equation of state

We present measurements of the excitation function of elliptic flow at midrapidity in Au+Au collisions at beam energies from 0.09 to 1.49 GeV per nucleon. For the integral flow, we discuss the interplay between collective expansion and spectator shadowing for three centrality classes. A complete excitation function of transverse momentum dependence of elliptic flow is presented for the first time in this energy range, revealing a rapid change with incident energy below 0.4 AGeV, followed by an almost perfect scaling at the higher energies. The equation of state of compressed nuclear matter is addressed through comparisons to microscopic transport model calculations.Comment: 10 pages, 4 eps figures, submitted for publication. Data files will be available at http://www.gsi.de/~fopiwww/pub

Impaired Brain Dopamine and Serotonin Release and Uptake in Wistar Rats Following Treatment with Carbotplatin

Chemotherapy-induced cognitive impairment, known also as “chemobrain”, is a medical complication of cancer treatment that is characterized by a general decline in cognition affecting visual and verbal memory, attention, complex problem solving skills, and motor function. It is estimated that one-third of patients who undergo chemotherapy treatment will experience cognitive impairment. Alterations in the release and uptake of dopamine and serotonin, central nervous system neurotransmitters that play important roles in cognition, could potentially contribute to impaired intellectual performance in those impacted by chemobrain. To investigate how chemotherapy treatment affects these systems, fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes was used to measure dopamine and serotonin release and uptake in coronal brain slices containing the striatum and dorsal raphe nucleus, respectively. Measurements were taken from rats treated weekly with selected doses of carboplatin and from control rats treated with saline. Modeling the stimulated dopamine release plots revealed an impairment of dopamine release per stimulus pulse (80% of saline control at 5 mg/kg and 58% at 20 mg/kg) after 4 weeks of carboplatin treatment. Moreover, Vmax, the maximum uptake rate of dopamine, was also decreased (55% of saline control at 5 mg/kg and 57% at 20 mg/kg). Nevertheless, overall dopamine content, measured in striatal brain lysates by high performance liquid chromatography, and reserve pool dopamine, measured by FSCV after pharmacological manipulation, did not significantly change, suggesting that chemotherapy treatment selectively impairs the dopamine release and uptake processes. Similarly, serotonin release upon electrical stimulation was impaired (45% of saline control at 20 mg/kg). Measurements of spatial learning discrimination were taken throughout the treatment period and carboplatin was found to alter cognition. These studies support the need for additional neurochemical and behavioral analyses to identify the underlying mechanisms of chemotherapy-induced cognitive disorders

A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study

<p>Abstract</p> <p>Background</p> <p>Because a large proportion of patients with panic attacks receiving approved pharmacotherapy do not respond or respond poorly to medication, it is important to identify additional therapeutic strategies for the management of panic symptoms. This article describes a randomized, rater-blind study comparing low-dose risperidone to standard-of-care paroxetine for the treatment of panic attacks.</p> <p>Methods</p> <p>Fifty six subjects with a history of panic attacks were randomized to receive either risperidone or paroxetine. The subjects were then followed for eight weeks. Outcome measures included the Panic Disorder Severity Scale (PDSS), the Hamilton Anxiety Scale (Ham-A), the Hamilton Depression Rating Scale (Ham-D), the Sheehan Panic Anxiety Scale-Patient (SPAS-P), and the Clinical Global Impression scale (CGI).</p> <p>Results</p> <p>All subjects demonstrated a reduction in both the frequency and severity of panic attacks regardless of treatment received. Statistically significant improvements in rating scale scores for both groups were identified for the PDSS, the Ham-A, the Ham-D, and the CGI. There was no difference between treatment groups in the improvement in scores on the measures PDSS, Ham-A, Ham-D, and CGI. Post hoc tests suggest that subjects receiving risperidone may have a quicker clinical response than subjects receiving paroxetine.</p> <p>Conclusion</p> <p>We can identify no difference in the efficacy of paroxetine and low-dose risperidone in the treatment of panic attacks. Low-dose risperidone appears to be tolerated equally well as paroxetine. Low-dose risperidone may be an effective treatment for anxiety disorders in which panic attacks are a significant component.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT100457106</p

HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q13

Background: We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD less than= 2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes. Methodology/Principal Findings: Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, pless than9.8x10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (pless than0.002, pless than0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas. Conclusions: We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both

Grasping isoluminant stimuli

We used a virtual reality setup to let participants grasp discs, which differed in luminance, chromaticity and size. Current theories on perception and action propose a division of labor in the brain into a color proficient perception pathway and a less color-capable action pathway. In this study, we addressed the question whether isoluminant stimuli, which provide only a chromatic but no luminance contrast for action planning, are harder to grasp than stimuli providing luminance contrast or both kinds of contrast. Although we found that grasps of isoluminant stimuli had a slightly steeper slope relating the maximum grip aperture to disc size, all other measures of grip quality were unaffected. Overall, our results do not support the view that isoluminance of stimulus and background impedes the planning of a grasping movement

Nutritional therapies for mental disorders

According to the Diagnostic and Statistical Manual of Mental Disorders, 4 out of the 10 leading causes of disability in the US and other developed countries are mental disorders. Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), addiction, and autism. The aim of this manuscript is to emphasize which dietary supplements can aid the treatment of the four most common mental disorders currently affecting America and other developed countries: major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD)

Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide

Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0) in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides), the anterior cingulate cortex (ACC: 6NS, 9S) and the nucleus accumbens (NAcc: 8NS, 13S). ANCOVA was used to control for age, gender, pH and RNA degradation, with P≤0.01 and fold change±1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A) and three were down-regulated in the NAcc (MT1F, MT1G, MT1H). Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain

A Dominant Negative ERβ Splice Variant Determines the Effectiveness of Early or Late Estrogen Therapy after Ovariectomy in Rats

The molecular mechanisms for the discrepancy in outcome of initiating estrogen therapy (ET) around peri-menopause or several years after menopause in women are unknown. We hypothesize that the level of expression of a dominant negative estrogen receptor (ER) β variant, ERβ2, may be a key factor determining the effectiveness of ET in post-menopausal women. We tested this hypothesis in ovariectomized nine month-old (an age when irregular estrous cycles occur) female Sprague Dawley rats. Estradiol treatment was initiated either 6 days (Early ET, analogous to 4 months post-menopause in humans), or 180 days (Late ET, analogous to 11 years post-menopause in humans) after ovariectomy. Although ERβ2 expression increased in all OVX rats, neurogenic and neuroprotective responses to estradiol differed in Early and Late ET. Early ET reduced ERβ2 expression in both hippocampus and white blood cells, increased the hippocampal cell proliferation as assessed by Ki-67 expression, and improved mobility in the forced swim test. Late ET resulted in either no or modest effects on these parameters. There was a close correlation between the degree of ERβ2 expression and the preservation of neural effects by ET after OVX in rats, supporting the hypothesis that persistent elevated levels of ERβ2 are a molecular basis for the diminished effectiveness of ET in late post-menopausal women. The correlation between the expression of ERβ2 in circulating white blood cells and brain cells suggests that ERβ2 expression in peripheral blood cells may be an easily accessible marker to predict the effective window for ET in the brain